Enalapril induces muscle epigenetic changes and contributes to prevent a decline in running capacity in spontaneously hypertensive rats

• Published in: Archives of gerontology and geriatrics 2025-02, Vol.129, p.105699, Article 105699
• Main Authors: Santos, Denis Carlos dos, Alves, Fernando Henrique Ferrari, Veríssimo, Luiz Fernando, Raquel, Hiviny Ataides, Volpini, Vinicius Lucca, Marques, Leonardo André da Costa, Martins-Pinge, Marli Cardoso, Fernandes, Karen Barros Parron, Andrade, Karoliny Coelho, Michelini, Lisete Compagno, Pelosi, Gislaine Garcia
• Format: Article
• Language: English
• Subjects: Angiotensin II receptor blocker; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotesin-converting-enzyme inhibitor; Animals; DNA methylation; DNA Methylation - drug effects; Enalapril - pharmacology; Enalapril - therapeutic use; Epigenesis, Genetic - drug effects; Hypertension - drug therapy; Hypertension - genetics; Losartan - pharmacology; Losartan - therapeutic use; Male; Muscle function; Muscle, Skeletal - drug effects; Rats; Rats, Inbred SHR; Renin-angiotensin system; Running - physiology
• ISSN: 0167-4943; 1872-6976; 1872-6976
• DOI: 10.1016/j.archger.2024.105699

•Enalapril reduced the rate of weight gain, reduced retroperitoneal fat, and lowered MAP.•Enalapril maintained distance running performance, even after the treatment ended.•Enalapril increased global DNA methylation in gastrocnemius muscle cells of SHRs.•Losartan treatment did not show significant effects on the measured parameters. Drugs such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can improve muscle function and exercise capacity, as well as preventing, attenuating or reversing age-related losses in muscle mass, however, the exact mechanisms by which these drugs affect muscle cells, are not yet fully elucidated. Moreover, the potential epigenetic alterations induced in skeletal muscle tissue are also largely unexplored. The aim of this study was to evaluate if enalapril or losartan can change the physical performance and epigenetic profile of skeletal muscle in spontaneously hypertensive rats (SHRs). Male SHRs were treated with water, enalapril (10/mg/kg/day) or losartan (10/mg/kg/day) for 28 consecutive days and submitted to progressive testing on a treadmill. Body weight, perigonadal and retroperitoneal fat, mean arterial pressure, heart rate, running distance and global DNA methylation in the gastrocnemius and soleus muscles were evaluated. Enalapril reduced the rate of weight gain, as well as reducing retroperitoneal fat (p < 0.05) and MAP (p < 0.05) and avoiding the decline in running distance when compared to the other groups (p > 0.05), even 7 days after the end of treatment (p > 0.05). Moreover, enalapril increased global DNA methylation in gastrocnemius muscle cells (p < 0.01). No effects were observed in the losartan-treated group. Our data showed that enalapril prevented the decline in physical function in SHR, as well as reduced the rate of weight gain of the animals. In addition, the results showed, alterations in the global DNA methylation of skeletal muscle cells skeletal structures of the gastrocnemius muscle.